To determine the risk of mortality associated with cardiometabolic risk factors in a national sample of adolescents and young adults. Prospective study of participants in the third NHANES (1988-1994), aged 12 to 39 years at the time of the survey (n = 9245). Risk factors included 3 measures of adiposity, glycated hemoglobin (HbA1c) level, cholesterol levels, blood pressure, self-reported smoking status, and cotinine level. Death before age 55 (n = 298) was determined by linkage to the National Death Index through 2006. Proportional hazards models, with age as the time scale, were used to determine the risk of death before age 55 years after adjusting for gender, race/ethnicity, and presence of comorbid conditions. After adjusting for age, gender, and race/ethnicity, results of categorical analyses showed that current smokers were at 86% greater risk for early death than those classified as never smokers; that those with a waist-to-height ratio >0.65 were at 139% greater risk than those with a WHR <0.5; and that those with an HbA1c level >6.5% were at 281% greater risk than those with an HbA1c level <5.7%. Neither high-density lipoprotein nor non-high-density lipoprotein cholesterol measures were associated with risk for early death. Our finding that risk for death before age 55 among US adolescents and young adults was associated with central obesity, smoking, and hyperglycemia supports reducing the prevalence of these risk factors among younger US residents.